Aquaporins, Colonic Water Transport, and Functional Constipation
Year: 2026
Type: article
Abstract: Functional constipation (FC) is a common disorder of gut–brain interaction whose clinical signature, hard, infrequent stools, points to disturbed colonic water handling. Aquaporins (AQPs) provide the transcellular route for transepithelial water movement in the colon, and evidence links AQP dysregulation to FC and slow-transit constipation (STC). This narrative review synthesizes human tissue studies, animal models, and in vitro experiments on colonic AQPs in constipation. Limited human tissue studies report segment-specific changes in AQP abundance. AQP3 is upregulated in the ascending colon, whereas AQP9 is downregulated in the descending colon. AQP4 is elevated in STC and correlates with stool consistency and colonic transit time. AQP8 is upregulated and undergoes osmotic-stress-driven translocation to the apical (luminal) membrane. A broader mucosal survey additionally found reduced AQP1, AQP7, AQP10, and AQP11 in FC. Experimental models add mechanistic insight but reveal no conserved direction of AQP change. Because AQPs conduct water passively down osmotic gradients, channel abundance cannot be equated with channel-mediated water flux. Regulatory pathways, including macrophage-derived prostaglandin E2 (PGE2), cytokines, microbial metabolites, and enteric neurotransmitters, converge on the AQP network, with AQP3 as a recurrent node. The available evidence supports an association between AQP dysregulation and the constipated phenotype without establishing causality. Functional readouts of transepithelial water movement in patients are needed before AQP modulation can be translated into therapy.
Authors: Kai Zheng, Rui Li, Wenyue Ma, Daqing Sun
Institution: Tianjin Medical University General Hospital
Language: English
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W7225654616